The major objective is to define the degree and character of the variability in plasma steady-state levels of imipramine and desmethylimipramine and to elucidate the relationship between this variability and clinical course. The protocol involves the multiple administration of a constant, oral dose of imipramine to a large sample (N 60) of depressed patients while serial measures of affective state are recorded. In addition, this study will examine both a) the pharmacodynamics of the drug including protein binding, half-life, apparent volume of distribution and body pool in order to clarify their relationship to clinical response. b) The characteristics of a depressive population that might allow a prediction of drug response. These characteristics will include phenomenologically genetic, and physiological parameters.